Primary Peritoneal Carcinoma Diagnosed During Prophylactic Bilateral Salpingo-Oophorectomy for a BRCA-1 –Positive Patient

Introduction

BRCA-positive carriers are identified as having an increased risk of developing ovarian, breast, and/or primary peritoneal cancer. Risk-reducing surgery is currently the leading option for any patient with a positive BRCA mutation. ¹ Prophylactic bilateral salpingo-oophorectomy (BSO) is an effective risk-reducing surgery for preventing the development of ovarian cancer by both removing the source of the malignancy prior to preneoplastic changes while also facilitating the early detection of ovarian malignancy in women with BRCA-1 and BRCA-2 mutations. The Prevention and Observation of Surgical Endpoints (PROSE) study reported a 53% reduction in breast-cancer risk and a 96% reduction in ovarian-cancer risk among BRCA-1 and BRCA-2 mutation carriers who had prophylactic BSO, compared to matched controls. ¹

The largest series review to date was published in 2016 in BMC Cancer, which evaluated the utility of pelvic-washing cytology (PWC) in patients with BRCA-1 or BRCA-2 mutations and determined that PWC is of little value for early detection of primary peritoneal cancer in patients undergoing risk-reducing salpingo-oophorectomy. ² It was also reported that 2 of 836 (0.24 %) patients with positive PWC developed concomitant primary peritoneal cancer. No patients developed subsequent primary peritoneal cancer. When malignant cytology samples were present (1.5%), malignancy was subsequently found in the ovaries and/or fallopian tubes. ²

Additionally, researchers determined that malignant PWC samples failed to add any value to histopathologic examination for detecting ovarian and/or fallopian-tube cancer when using the sectioning and extensively examining of the fimbriated end (SEE-FIM) protocol. In the SEE-FIM protocol, the greatest surface area of the tube is histologically examined, based on the suggestion that multiple deeper sections should be examined, if the initial hematoxylin and eosin sections are negative. ³

This article is a case report of a 60-year-old female who underwent risk-reducing BSO for her BRCA-1–positive status, and in whom PWC returned an incidental finding of primary peritoneal adenocarcinoma.

Case

The patient was a 60-year-old gravida 3, para 2012, of Ashkenazi Jewish heritage with a history of recurrent triple-negative infiltrating ductal carcinoma of the breast and a known BRCA-1–positive mutation (187delAG BRCA1:deleterious), status post a bilateral mastectomy, breast reconstruction, and chemotherapy with 1 year of tamoxifen. She presented for laparoscopic risk-reducing BSO. Her cancer antigen–125 (CA-125) level was within normal limits prior to surgery and she had no history of abnormal Papanicolaou smears or irregular menses. A transvaginal ultrasound showed a normal retroverted 50-cc uterus with an endometrial thickness of 1.5 mm.

She reported no recent weight loss, night sweats, fevers, nor other symptoms that would have been suspicious for malignancy. There were no pertinent physical examination findings. This patient's past medical history, however, was significant for cryoglobulinemia, hypertension, Sjögren's syndrome, and systemic lupus erythematosus. Her family history included breast cancer in her mother at age 40.

A laparoscopic BSO with omental biopsy was performed uneventfully with no gross abnormality of the fallopian tubes, ovaries, or peritoneum identified. Pelvic washings were sent to cytology. The final cytologic analysis revealed positive malignant adenocarcinoma cells. Extensive pathologic evaluation using the SEE-FIM protocol of the bilateral salpinx fimbriated ends and ovaries did not show any malignancy. Postoperative computed tomography/positron emission tomography scans of the chest/ abdomen/pelvis were also negative. A subsequent endometrial biopsy was within normal limits showing a benign endocervix.

Results

This patient's case was presented at a tumor board for review. As isolated peritoneal carcinoma is rare and the prognosis and treatment is unknown, a decision was made for her to undergo chemotherapy with carboplatin and paclitaxel for 6 cycles. She received gemcitabine and carboplatin for 6 cycles q21d secondary to severe peripheral neuropathy. This patient recovered well with no current evidence of any recurrence.

Discussion

Primary peritoneal carcinoma is a rare primary tumor that was historically classified as a “carcinoma of unknown primary” and that is believed to arise from extraovarian peritoneum with Müllerian potential. ⁴ Eltabbakh et al. reported that women with primary peritoneal cancer were older than women with primary ovarian cancer at a mean age of 61 years old. ⁵ Patients typically have advanced disease at the time of presentation, with symptoms of abdominal pain and distention with ascites, histology, and response to chemotherapy that is similar to ovarian cancer. ⁶ Diagnostic criteria to distinguish primary peritoneal cancer from primary ovarian cancer include: normal-size ovaries; extraovarian-site involvement greater than surface involvement of the ovary; an ovarian component, at most, <5 × 5 mm within the ovary and otherwise confined to the surface of the ovary; and histologically predominantly serous. ⁷ Reports of primary peritoneal cancer suggest that serum CA-125 is a useful tumor marker for monitoring the course of primary peritoneal cancer.^6–8 However in the current patient, the initial CA-125 level was within normal limits.

In this case, the patient was at risk for primary peritoneal cancer due to her BRCA-1–mutation status; however, she did not show any physical or symptomatic signs of occult malignancy at the time of her procedure. BRCA-positive carriers are known to have an increased risk of developing ovarian, breast, and/or primary peritoneal cancer. ¹ Prophylactic BSO is suggested for these women in order to prevent the development of ovarian cancer by removing the source of the malignancy prior to preneoplastic changes and to also potentially allow for early detection of ovarian malignancies. In a review of the literature, 836 patients underwent risk reducing salpingo-oophorectomy for BRCA-positive status, with just 2 cases of primary peritoneal cancer identified. Due to these results, it was determined that malignant PWC samples failed to add any value to histopathologic examination for detecting ovarian and/or fallopian-tube cancer when using the SEE-FIM protocol. ²